Controllable exposure chamber for biological specimens

Abstract

A system for gas sensing of a biological sample may include a chamber, for example, containing a biological sample therein. The system may also include a gas sensing unit coupled to the chamber and separated from the chamber by a movable separator. When the separator is modified or moved, a gas sensor included in the gas sensing unit may be selectively exposed to a fluid headspace of the first chamber, such as a gaseous environment associated with the biological sample.

Description

[0001] Claiming priority

[0002] This application claims priority to U.S. Provisional Application Serial No. 63 / 370,225, filed on August 2, 2022, the entire contents of which are incorporated herein by reference. Background Art

[0003] A blood culture is a sample of blood submitted to a microbiology laboratory for the purpose of identifying organisms in the blood that may be causing bacterial, fungal, or other infections. Blood culture results can be used to determine the appropriate course of antibiotic therapy and / or source of infection and help rule out sepsis and other infections. Blood culture results can also help identify specific pathogens to aid in treating patients with more specific infections. The process of obtaining a blood culture may involve drawing a blood sample and packaging the blood sample in a vial for transportation to a microbiology laboratory for analysis of the blood sample.

[0004] A blood culture bottle can include a sample collection fluid and a nutrient medium that is mixed with the blood sample stored in the blood culture bottle. The vial containing the blood sample can be stored at a specific temperature until it reaches a microbiology laboratory, where the vial is examined to determine if one or more organisms are present in the blood sample. If the culture shows that a microorganism, such as bacteria, is present in the blood sample, other tests can be performed to determine more detailed information about the microorganism and how to best treat the patient.

[0005] Microorganisms, such as bacteria or fungi, present in a blood sample or other sample can be identified based on their type. By using specific culture tests, such as blood cultures, patients can receive specific types of treatment based on the strains of bacteria found in the blood sample. Blood culture bottles containing blood samples can be shipped to a microbiology laboratory where organisms can be grown and identified from the blood sample.

[0006] Similar methods can be used to identify cultures from other biological specimens, such as cerebrospinal fluid, pleural fluid, and spinal fluid, as well as cultures of other body fluids such as urine, sputum, throat swabs, eye swabs, wounds, body fluids, or secretions. Summary of the invention

[0007] Biological specimens may be contained within vials that are to be tested, such as for specific cultures or other types of biochemical or biological tests. Such testing can often be performed using manual procedures that can take anywhere from a few hours to a few weeks, during which time the culture bottles cannot be used for other purposes (e.g., transferring samples from positive blood culture bottles to culture dishes for additional culture and isolation of microorganisms). To do this, technicians often must transfer the contents from the original container to another container for subsequent testing (e.g., incubating the sample for isolation and identification, or performing antibiotic susceptibility testing). The process of transferring the contents of a culture bottle to another container is labor intensive and has a number of associated contamination risks for both the technician and the biological specimen. Furthermore, after the contents of the culture bottle have been transferred to a different container, they may be read using a manual visual procedure. This can introduce a number of sources of error, including the technician having to read the vial incorrectly, the technician having to interpret a mislabeled vial, or the technician having to read a non-optimal location on the vial that does not correspond to a positive growth site on the vial.

[0008] In another approach, a gas sensor or gas sensor array can be used to detect gases produced by bacteria. A vial can receive a biological sample. The vial can be connected to a gas sensor for detecting the presence of bacteria in a culture fluid. If the gas sensor array detects the presence of bacteria, then the technician will also need to time-consumingly transfer some of the contents of the culture bottle to a separate container, which requires manual removal from the gas sensor device in order to access the contents of the bottle. The inventors have recognized that a technology is needed to quickly detect gases from a biological sample in a container and eliminate some of the manual operations required by other methods. For example, the gas sensor can be separated from the biological sample fluid. The gas sensor can be selectively exposed to a gas environment associated with the biological sample.

[0009] This document describes a gas sensing system including a liquid-protected gas sensor. Such a system may include or use a first chamber and a second chamber carrying the gas sensor, the first chamber being used to hold a biological sample therein. For example, the gas sensor may be isolated from the first chamber by an openable seal to convert from a first state to a second state when the seal is opened, thereby allowing gas from the first chamber to diffuse or otherwise flow into the second chamber for sensing by the gas sensor. The second chamber may be isolated from the surrounding environment in at least the second state. The gas sensor may include or use a field effect transistor (FET), such as a carbon nanotube FET (CNFET). In addition, the gas sensor may include or use a camera, a spectral imaging sensor, a hyperspectral imaging sensor, a colorimetric imaging sensor, a fluorescence response imaging sensor, or a colorimetric sensor.

[0010] The openable seal can be closed in a first state, wherein the second pressure in the second chamber is positive relative to the first pressure in the first chamber. In addition, the seal can include a first component that can be moved relative to the second component to provide at least one opening in the seal, thereby switching from the first state to the second state. The openable seal can be included in a kit with a second seal that can be exchanged with the first seal. For example, the system can include a seal perforator that can be actuated to destroy the openable seal, thereby switching from the first state to the second state. The openable seal can include a breathable membrane to prevent liquid from flowing through. The openable seal can include a closable port of the first chamber. In the first state, the movement of gas through the closable port can be physically hindered, while in the second state, the movement of gas through the closable port can be provided. In one example, the first chamber can be included as part of the second chamber plug. Here, the size and shape of the second chamber plug can be designed to interface with the second chamber to fluidically close the second chamber by blocking the opening of the second chamber.

[0011] Each non-limiting example described herein may stand alone or in various permutations or combinations with one or more other examples.

[0012] This summary is intended to provide an overview of the subject matter of this patent application. It is not intended to provide an exclusive or exhaustive explanation of the invention. The detailed description is included to provide more information. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] In the accompanying drawings, which are not necessarily drawn to scale, the same numerals may describe similar components in different views. Similar numerals with different letter suffixes may represent different instances of similar components. The accompanying drawings generally illustrate various embodiments discussed in this document by way of example and not limitation.

[0014] Figure 1A An example of a fluid transfer system is depicted.

[0015] Figure 1B A perspective view of a device for facilitating fluid transfer is shown.

[0016] Figure 1C A side view of a device for facilitating fluid transfer is shown.

[0017] Figure 2 An example of a gas sensing system is depicted.

[0018] Figure 3 Another example of a gas sensing system is depicted.

[0019] Figure 4A An example of a gas sensing system is depicted in a first position.

[0020] Figure 4B An example of a gas sensing system is depicted in a first position.

[0021] Figure 5 is a flow chart describing a method of using a gas sensing system. DETAILED DESCRIPTION

[0022] Biological specimens, such as human blood samples, can be placed in vials for culture testing. One approach to testing cultures is to place several different specimens in separate containers, such as vials. Technicians then perform multiple manual operations, such as opening the containers, adding reagents, mixing the samples, and incubating the samples. After incubation, the technician visually assesses the individual vials for the presence of the target culture to determine the test result. This can introduce many sources of error, including the technician having to read the vial incorrectly, the technician having to interpret a mislabeled vial, or the technician having to read a non-optimal location on the vial that does not correspond to a positive growth site on the vial. Another challenge with this approach is that results are often not certain for days or weeks after the biological specimen is extracted from a human patient. Additionally, performing this multiple manual operations can result in sample loss, reagent waste, cross-contamination, and other errors in sample preparation.

[0023] In another method of testing biological samples, a gas sensor can be used to check the biological sample. Here, a vial can hold the biological sample, and one end of the vial can be sealed. The other end of the vial can be connected to a gas sensor, which can be placed in a culture fluid (or in fluid communication with the culture fluid). The gas sensor can detect when the culture fluid changes, thereby detecting when bacteria are detected in the culture fluid. One challenge of this method is that the gas sensor may be damaged by the biological sample. For example, a liquid biological sample can cause corrosion, dilution, electrical short circuit or blockage of the gas sensor, thereby degrading the gas sensor. In addition, this method may involve manual operations similar to those described above, such as transferring the culture bottle to a separate container, and involving a technician removing the culture bottle from the sensor when a change in the culture fluid is detected.

[0024] The inventors have recognized techniques for processing and examining biological samples within containers that do not require certain manual operations of other methods. For example, a gas sensor can be separated from the biological sample fluid contained in a first chamber. When a separator such as a seal is modified or moved, the gas sensor can be selectively exposed to the fluid head space of the first chamber, such as a gas environment associated with the biological sample. For example, the gas sensor can be located within a plug or lid of a container including the first chamber. The action of coupling the plug or lid to the container can be used to manipulate the separator so that the gas sensor is exposed to the gas head space of the first chamber. In addition, the gas sensor can be located within a second chamber, and the first and second chambers can be arranged in the same container. Here, when the separator is modified or moved, the first chamber and the second chamber can be selectively fluidly connected, such as exposing the gas environment associated with the liquid biological sample to the gas sensor.

[0025] Figure 1A An example of a fluid transfer system is depicted. The fluid transfer system 100 may include a sample container 110, such as a vial, for receiving and holding a biological sample 114 therein. The fluid transfer system 100 may involve selectively exposing the biological sample 114 with a sensor or sensing system, for example, to monitor the growth or condition of the biological sample 114 while ensuring that the sample container 110 remains user-sealable and reducing contamination during incubation of the contents within the sample container 110.

[0026] The sample container 110 may include an openable, fluid-tight seal 115 at the sealing hole 113 of the sample container. For example, the fluid-tight seal 115 may include a diaphragm including, for example, silicone, rubber, or plastic attached (e.g., adhered or fastened) to the sample container 110. The seal 115 may provide a sterile environment within the sample container 110, for example, by preventing fluid, dust particles, or other bacteria from contaminating or accidentally entering the sample container 110. In one example, the seal 115 may include a gas-permeable membrane, such as polyethylene, polytetrafluoroethylene, or other types of film or membrane materials. The gas-permeable membrane may include liquid-impermeable properties, such as blocking the flow of liquid.

[0027] Typically, when a force (e.g., a piercing force) is applied to a flexible membrane (e.g., an elastic membrane) of the seal 115, the flexible membrane can define a passage to the interior of the sample container 110. For example, an injection needle (or some other piercing element) can be used to pierce the membrane. After the syringe is removed from the membrane, the membrane can be restored to its static, sealed or unperforated state (e.g., resealed). Resealing can prevent the biological sample 114 from leaking or escaping from the sample container 110. Such a biological sample 114 may include one or more of liquid, solid, colloid, and gaseous components. The biological sample 114 may include one or more liquids, such as blood, plasma, cerebrospinal fluid, synovial fluid, urine, sweat, saliva, transdermally obtained fluid (TTF), sputum, mucus, feces, gastric contents, and tissue. Although the fluid-impermeable seal 115 can facilitate certain fluid transfer techniques, such as extraction or deposition through a need or cannula, the seal 115 in an unopened, resealed, or partially sealed state can pose challenges to the cultivation and sensing of the biological sample 114.

[0028] In one example, the fluid transfer system 100 can include a device 120 for providing access to a sample container 110. In one example, the device 120 can irreversibly sever and open a fluid-tight seal 115 to facilitate fluid transfer between the sample container 110 and a culture or sensing system, such as located external to the sample container 110. For example, certain culture or sensing systems may involve fluid transfer, such as diffusion of a gas headspace, whose flow rate cannot be provided by a needle or cannula passing through the seal 115, such as due to constriction of the lumen of the needle or cannula. Therefore, the device 120 can help provide the desired fluid access to the sample container 110 by irreversibly severing and opening the fluid-tight seal 115 of the sample container while maintaining user resealability. This configuration helps adapt certain specialized devices (e.g., a blood bottle including a resealable septum configured for access by a syringe) to certain advanced detection and culture systems that may otherwise be incompatible or undesirable with a direct seal or septum of the container.

[0029] Figure 1B and Figure 1C Shows Figure 1A Detailed view of the device 120. The device 120 may include a fitting 102 sized and shaped to connect to the hole 113 of the sample container 110 (e.g., Figure 1AAs described herein, the fitting 102 can define a body of the device 120, and such body can be tightly pressed against the hole 113 of the sample container 110 to plug, fill or block the hole 113. For example, the fitting 102 can include a viscous material, such as an elastomer, which is arranged to limit the disengagement of the fitting 102 from the sample container 110. In addition, the fitting 102 can include a taper, such as a conical or stepped taper tip, for insertion into the hole 113. The fitting 102 can also include one or more retaining elements for retaining the fitting 102 on the sample container 110 and for maintaining a fluid seal between the fitting 102 and the hole 113.

[0030] In one example, the accessory 102 can be at least partially inserted into the hole 113. Coupling the accessory 102 to the hole 113 can establish a durable, semi-permanent, or permanent joint. For example, the joint may require a force greater than 5 Newtons (N) to break or pull out. Coupling the accessory 102 to the hole 113 can also involve irreversibly cutting and opening a fluid-tight seal 115. Here, the accessory 102 can include or be attached to a perforator 116, such as at or near the end of the accessory 102. The perforator 116 can be configured to irreversibly cut and open the seal 115, such as during the process of inserting the accessory 102 into the hole. For example, the perforator 116 can include a seal expander 117. The seal expander 117 can include ribs, fins, or concentric ridges for expanding the seal 115. The size and shape of the seal expander 117 can be such that when the perforator 116 is pushed toward the seal 115, the displacement of the expander 117 is greater than 20% of the surface area of ​​the seal 115, such as forming a seal opening whose cross-sectional area is at least 20% of the surface area of ​​the seal 115. In one example, the expander 117 can move more than 50% of the surface area of ​​the seal 115, such as forming a seal opening whose cross-sectional area is at least 50% of the surface area of ​​the seal 115. In one example, a pressure-actuated mechanism, such as a linear actuator or a solenoid, can be operably connected to the perforator 116 to move the perforator 116 to destroy the seal 115. Such a pressure-actuated mechanism can be actuated when exposed to a fluid pressure greater than a predetermined threshold level. In one example, the perforator 116 can be spring-biased to destroy the seal 115. The perforator 116 can be configured to be automatically actuated, such as by a timer-based or controller-based system.

[0031] The accessory 102 may include an inner cavity 119 extending between a first end and a second end of the accessory. The inner cavity 119 may extend toward the perforator 116 so that when the seal 115 is cut and opened by coupling the accessory 102 to the hole 113, the first end of the inner cavity 119 is connected to the head space 112 fluid of the sample container 110. For example, after the seal 115 is cut and opened by the perforator 116, the inner cavity 119 can establish an access port to the biological sample 114. In one example, the inner cavity 119 may include a cross-sectional diameter greater than about 2.5 millimeters (mm). For example, within the range of about 2.5 mm and about 2.5 centimeters (cm), or within the range of about 3 mm and about 2.5 centimeters. For example, the cross-sectional diameter can be significantly larger than the diameter of a conventional needle, such as greater than about 2 millimeters (mm).

[0032] The device 120 may also include a user-replaceable sealing housing 118. For example, the sealing housing 118 may be sized and shaped to accommodate at least one biological sample growth indicator 123 at the second end of the internal cavity 119. For example, the at least one biological sample growth indicator 123 is arranged to be enclosed by the sealing housing 118 and separated from the surrounding environment outside the sample container. The sealing housing 118 may be selectively engaged by a user to limit or capture fluid escaping from the second end of the internal cavity 119 of the fitting, such as after the seal is opened by the piercer 116. Thus, the sealing housing 118 may define a chamber or cavity for receiving a portion of the biological sample 114. In one example, the user-replaceable sealing housing 118 may include a removable cover that may be removably coupled to a coupling feature of the fitting 102. Here, the coupling feature may include threads on the fitting 102 or the removable cover, and the sealing housing 118 may be user-engageable to limit fluid from the second end of the internal cavity 119 by tightening the removable cover onto the fitting 102. The coupling features may also include, for example, other forms of engagement components, such as clamshell fittings, snap-fit ​​fittings, bayonet fittings, twist-fittings, or combinations thereof. In one example, at least one of the fitting 102 or the sealed housing 118 may be formed of a translucent or transparent material to allow imaging into the sample container while the sealed housing 118 remains engaged.

[0033] In one example, at least one biological sample growth indicator 123 may include a biological culture medium, such as nutrient agar. For example, the culture medium may be a label, paddle, or mini-plate of nutrient agar contained by the sealed housing 118 and arranged to contact the fluid from the sample container by passing the liquid from the sample container 110 through the inner cavity 119. Here, after the device 120 is coupled to the sample container 110, the sample container 110 may be inverted to allow the liquid to pass from the sample container 110 through the inner cavity 119 and contact the biological culture medium of the at least one biological sample growth indicator 123. This method of cell culture using a septum sealed container allows monitoring of cell culture even in situations where liquid culture monitoring technology is not available or feasible. Therefore, the biological sample growth indicator 123 including the biological culture medium helps to adapt certain specialized equipment, such as a blood bottle including a resealable septum configured to be entered by a syringe, to situations where available monitoring equipment is limited.

[0034] In one example, at least one biological sample growth indicator 123 may include a gas sensor. The gas sensor may include, for example, a semiconductor-based gas sensor, such as a field effect transistor (FET), such as a carbon nanotube FET (CNFET), a silicon carbide FET (SiCFET), a metal oxide semiconductor FET (MOSFET), a graphene FET (GFET), a transition metal disulfide FET (TMDFET), or a black phosphorus FET (BPFET). In addition, the gas sensor may include a polymer-based gas sensor, an optical gas sensor, a color gas sensor, an atomic absorption spectrometer, a catalytic gas sensor, a catalytic combustion gas sensor, an electrochemical sensor, a resistive gas sensor, and the like. At least one biological sample growth indicator 123 may also include or use a camera, a spectral imaging sensor, a hyperspectral imaging sensor, a colorimetric imaging sensor, or a fluorescence response imaging sensor. The gas sensor may also include at least one light-emitting illumination element and at least one light-receiving photodetector or other element, so that the gas sensor 125 can be used as a photoelectrochemical sensor.

[0035] In one example, at least one biological sample growth indicator 123 may include an internal fluid sensor for measuring at least one fluid condition within at least one of the inner cavity 119 or the sample container 110. In one example, the device 120 may also include an electrical contact 121 located outside the sample container 110, such as electrically coupled to the internal fluid sensor. In one example, the electrical contact 121 may transmit the internal fluid sensor data to an external location while the sealed housing 118 remains engaged to restrict fluid from escaping from the second end of the inner cavity 119.

[0036] Back to Figure 1A, the system 100 may include or be used with a sample container plug 122 that is sized and shaped to be removably connected to the hole 113 of the sample container 110. The size and shape of the device 120 may be designed to replace the sample container plug 122 during connection to the sample container 110. In addition, the system 100 may include or be used with a sample container plug replacement device for removing the sample container plug 122 from the hole 113 of the sample container 110 and replacing the chamber plug with the device 120. Here, the chamber plug replacement device may be configured to lift, raise, slide, roll, or otherwise move the sample container plug 122 away from the hole 113 of the sample container 110 to facilitate replacing the sample container plug with the device 120. For example, the chamber plug replacement device may remove the sample container plug 122 from the sample container 110 and replace the sample container plug with the device 120 simultaneously or sequentially. The sample container plug 122 or the device 120 may be removably coupled to the hole 113 of the sample container 110 by a corresponding coupling member. In one example, the coupling member may be sized and shaped to be removably coupled to the aperture 113 of the sample container 110 via threads, snap fit, press fit, flange, bayonet fit, pin-and-slot coupling, clamp fit, or other releasable coupling means.

[0037] Figure 2 An example of a gas sensing system is depicted. The gas sensing system 200 is similar in many respects to the gas sensing system 100 described above. The gas sensing system 200 may include or use a biological sample container 250 that includes a first chamber 210 for containing a liquid biological or another sample sealed therein. The biological sample container 250 may also include a second chamber 230 carrying a gas sensor 225 and a fluid conduit 224 that may be connected between the first chamber 210 and the second chamber 130. A separator 215 may be included between the first chamber and the second sensor, such as within the fluid conduit 224. In one example, the separator 215 may be manipulated to convert the container 250 from a first state to a second state, such as allowing gas from the first chamber 220 to diffuse or otherwise flow into the second chamber 230 so that it is sensed by the gas sensor 225 when the biological sample is located in the first chamber 210. Such a biological sample container 250 may help, for example, a biological sample 214 including a liquid component to be prepared, processed, and sensed or imaged at a later time without damaging the gas sensor or exposing the gas sensor 225 or the sample 214 to the surrounding environment.

[0038] The separators discussed herein, such as separator 215, may include at least one feature for manipulating the gas sensing system, such as a threaded mechanism, a threaded shaft mechanism, a pinion mechanism, a rack mechanism, or a cam mechanism. Such a mechanism may allow an operator to manually open or close the system by moving or changing the separator. In addition, one or more locking features may be included to help ensure that the separator remains open or remains closed, transitioning from a first state to a second state, or vice versa. For example, a locking feature may be positioned at an opening of the separator, at a pin that engages the separator, or at an axis that rotates to engage the separator.

[0039] The separators discussed herein may also include a plurality of openings (e.g., a plurality of slits, holes, etc.) that may be aligned with one another. The openings may also be configured to mate with one another, such as corresponding openings of the first component and the second component. In addition, the separators discussed herein may include at least one resilient component, such as an elastomeric material, to allow an operator to manually deform (e.g., move) the separator without requiring a large actuation force.

[0040] Figure 3 Another example of a gas sensing system is depicted. The gas sensing system 300 may include or use a fluid switch 352 to selectively connect a gas headspace 312 between a first container 310 (e.g., a sample bottle) including a biological sample 314 and a second container 330 (e.g., a gas sensing bottle) including a gas sensor 325. Here, each of the first container 310 and the second container 330 can be fluidly sealed relative to the surrounding environment. The conduit 324 can be fluidly connected to a peristaltic pump or other pump of the fluid switch 352 to enable gas exchange from the first container 310 to the second container 330. In one example, the fluid switch 352 can include a filter or filter assembly to filter out particulate matter and bacteria from the fluid drawn from the first container 310. The fluid switch 352 can include a mechanism to selectively open a valve connecting the conduit 324 to the pump.

[0041] Alternatively or additionally, the gas sensing system 300 can include a siphon to provide suction for drawing at least a portion of the liquid of the biological sample 314 into the fluid exchanger 352 or the second container 330. Here, the inlet of the conduit 324 can be at least partially immersed in the liquid portion of the biological sample 314 in the first container 310.

[0042] The controller 354 (e.g., a microprocessor, a microcontroller, or a single-chip microcomputer) can be configured to control the operation of the fluid switch 352. The controller 354 can receive an initial signal from a sensor (e.g., a gas sensor 325) to start a sequence (e.g., start fluid exchange), and can include a signal detector and a timing mechanism to determine the duration of the sequence. The fluid handling components, such as the valve assembly 356, can be selectively controlled by the controller to guide the flow of fluid using the fluid switch 352. For example, the valve assembly 356 can be controlled to open the valve to guide the fluid from the first container 310 to the second container 330, and can be controlled to close the valve to block the flow of fluid within the fluid switch 352. In addition, the two-way valve assembly 356 can be fluidly connected to the conduit 324 and selectively controlled by the controller 354 to allow the fluid using the fluid switch 352 to flow from the conduit 324 into the second container 330. In this way, the gas environment associated with the biological sample 314 in the first container 310 can be sucked into the second container 330. The pressure in the second container 330 may be set by the controller 354 to be the same as the pressure in the first container 310. In addition, the controller 354 may control the time of the suction or the flow rate of the fluid.

[0043] The controller 354 (e.g., a microprocessor, a microcontroller, or a single-chip microcomputer) can be configured to control the operation of the fluid switch 352. The controller 354 can receive an initial signal from a sensor (e.g., a gas sensor 325) to start a sequence (e.g., start fluid exchange), and can include a signal detector and a timing mechanism to determine the duration of the sequence. The fluid handling components, such as the valve assembly 356, can be selectively controlled by the controller to guide the flow of fluid using the fluid switch 352. For example, the valve assembly 356 can be controlled to open the valve to guide the fluid from the first container 310 to the second container 330, and can be controlled to close the valve to block the flow of fluid within the fluid switch 352. In addition, the two-way valve assembly 356 can be fluidly connected to the conduit 324 and selectively controlled by the controller 354 to allow the fluid using the fluid switch 352 to flow from the conduit 324 into the second container 330. In this way, the gas environment associated with the biological sample 314 in the first container 310 can be sucked into the second container 330. The pressure in the second container 330 may be set by the controller 354 to be the same as the pressure in the first container 310. In addition, the controller 354 may control the time of the suction or the flow rate of the fluid.

[0044] In one example, the second container 330 including the gas sensor 325 can be evacuated prior to fluidly connecting to the gas headspace 312 of the first container 310. For example, the second container 330 can be evacuated to a pressure less than ambient pressure, less than 100 mm Hg, less than 20 mm Hg, or less than 10 mm Hg, less than 5 mm Hg, less than 2 mm Hg, less than 0.5 mm Hg, less than 0.1 mm Hg, less than 0.05 mm Hg, or less than 0.01 mm Hg. The controller 354 can control the duration of the evacuation sequence (e.g., from about 15 seconds to about 2 hours) and / or the rate at which gas is evacuated from the first container 310.

[0045] In one example, a new, unopened or otherwise cleaned second container 310 (e.g., a gas sensing bottle) can be provided or obtained for testing a single biological sample 314. In addition, the second container 310 can be reused for gas sensing of at least two different biological samples. Here, in order to avoid contamination of subsequent biological samples by residues of the first biological sample, for example, the second container 310 can be cleaned. Cleaning may involve a variety of methods, such as the use of cleaning agents such as saline (NaCl), buffered aqueous solutions (such as 5× or 10× TBE) and organic solvents such as methanol, ethanol, ethyl acetate and chloroform. Other cleaning methods can be used, such as chemical removal (e.g., by acid or alkali), physical removal (e.g., by laser or heat), electrochemical removal (e.g., by using electricity and / or salt solutions) and combinations of these methods. In addition, the cleaning agent can include ingredients such as biocides, chelating agents, protein binders, surfactants, enzymes and / or antimicrobial agents (e.g., antimicrobial agents effective against certain bacteria and fungi) or any combination thereof. In one example, the fluid switch 352 can help facilitate this cleaning of the second container 330 , such as through an automated process controlled by the controller 354 .

[0046] Figure 4A and Figure 4BAn example of a gas sensing system is depicted. The gas sensing system 400 can be similar to the gas sensing system 100 described above. Here, the separator can include or use an openable seal 415. In one example, the gas sensing system 400 can include a closable port 432. The gas sensing system 400 can include a first component 426 that can move relative to a second component 428 so as to provide at least one selectively controllable opening therebetween that can be used to convert the gas sensing system 400 from a first state to a second state. For example, in the first state, the chamber 430 of the second component 428 can be fluidly isolated from the closable port 432 of the first component 426. In the second state, the chamber 430 of the second component 428 can be fluidly connected to the closable port 432 of the first component 426. The first component 426 can, for example, be coupled to a shaft that can move axially and / or pivotally relative to the second component 428.

[0047] like Figure 4A As shown, the first component 426 can be at least partially coupled to the second component 428 while maintaining isolation between the chamber 430 and the port 432 in the first state. Here, the port 432 can be closed, such as being blocked from the chamber 430 by the wall of the second component 428. Alternatively or additionally, the openable seal can block the chamber 430 from the port 432 fluidly, such as whether the port 432 is closed or open. In one example, the first component 426 can include or use a seal piercer 416. The seal piercer 416 can include, for example, a sharp point or edge that can pierce the openable seal 415, thereby opening a fluid path between the closable port 432 and the chamber 430. In addition, at least one of the first component 426 or the second component 428 can include or use a piercing stopper 417, such as a standoff, tab, protrusion, protrusion, notch, or ridge, which is configured to abut against the first component 426 or the second component 426 and prevent the first component 426 and the second component 428 from moving closer toward each other. For example, the piercer stop 417 can help prevent the sealing piercer 416 from piercing the second component 428. The first component 426 or the second component 428 can also include or be coupled to a power source, for example, to provide current to the one or more gas sensing elements 425.

[0048] For example, when the gas sensing system 400 is moved from the first position ( Figure 4A shown) moves to the second position ( Figure 4B432), the seal perforator can be driven toward the openable seal 415 while the port 432 is moved to the open position. For example, when at least one of the first component 426 and the second component 428 is moved relative to each other toward the second position, the gas sensing system 400 can move from the first state to the second state. Here, the fluid can flow between the port 432 and the chamber 430, and the port 432 can fluidly connect the chamber to another container including the biological sample. Therefore, when the system 400 moves toward the second state, one or more gas sensing elements 425 can be exposed to a gas environment associated with the biological sample.

[0049] Figure 5 is a flow chart describing a method of using a gas sensing system.

[0050] At 510, the method may include containing a biological sample in a first container. At 520, the method may include providing a gas sensor in a second container, the gas sensor being isolated from the second container by an openable seal. At 530, the method may include converting from a first state to a second state by opening the openable seal to allow gas from the first container to diffuse or otherwise flow into the second container for sensing by the gas sensor, while the biological sample may be located in the first container. The second container may be isolated from the surrounding environment in at least the second state. For example, the conversion may include piercing the openable seal. The conversion may also include moving a first part of the openable seal relative to a second part of the openable seal to provide at least one opening in the seal. In addition, the conversion may include replacing the openable seal with a second seal. At 540, gas sensing may be performed by the gas sensor when the first and second chambers are converted to the second state.

[0051] The above detailed description may include references to the accompanying drawings that form a part of the detailed description. The accompanying drawings illustrate specific embodiments in which the present invention can be practiced by way of illustration. These embodiments are also referred to as "examples" in this article. These examples may include elements other than those shown or described. However, the inventors also consider examples that only provide the shown or described elements. In addition, the inventors also consider examples of any combination or permutation of those elements (or one or more aspects thereof) shown or described, whether with respect to a specific example (or one or more aspects thereof), or with respect to other examples (or one or more aspects thereof) shown or described herein.

[0052] In the event of an inconsistency in usage between this document and any document incorporated by reference, the usage in this document controls. In this document, the terms "including" and "in which" are used as the plain English equivalents of the respective terms "comprising" and "wherein." Furthermore, in the following claims, the terms "including" and "comprising" are open-ended, that is, a system, apparatus, article, composition, formulation, or method that may include elements other than those listed after the term in a claim is deemed to be within the scope of the claim.

[0053] In this document, the terms "a" or "an" are used to include one or more, as is common in patent documents, independent of any other instances or uses of "at least one" or "one or more". In this document, the term "or" is used to refer to non-exclusivity, or "A or B" may include "A but not B", "B but not A", and "A and B", unless otherwise noted. In this document, the terms "including" and "wherein" are used as the plain English equivalents of the respective terms "comprising" and "wherein". In addition, in the following claims, the terms "including" and "comprising" are open-ended, that is, systems, devices, articles, compositions, preparations, or methods that may include additional elements in addition to the elements listed after the term in the claim are still deemed to fall within the scope of the claim. In addition, in the following claims, the terms "first", "second", and "third", etc. are used merely as labels and are not intended to impose numerical requirements on their objects.

[0054] The above description is intended to be illustrative rather than limiting. For example, the above examples (or one or more aspects thereof) may be used in combination with each other. Other embodiments may be used, such as those that are of ordinary skill in the art may use after reading the above description. The abstract is provided to allow the reader to quickly determine the nature of the technical disclosure. The premise of submitting this document is that this document shall not be used to interpret or limit the scope or meaning of the claims. In addition, in the above detailed description, various features may be combined together to simplify the disclosure. This should not be interpreted as meaning that unclaimed public features are essential to any claim. On the contrary, the subject matter of the present invention may be less than all features of a particular disclosed embodiment. Therefore, the following claims are incorporated into the detailed description as examples or embodiments, each claim exists independently as a separate embodiment, and it is conceivable that these embodiments may be combined with each other in various combinations or arrangements. The scope of the present invention should be determined with reference to the attached claims and the full scope of equivalents enjoyed by these claims.

Claims

1. An apparatus for providing access to a biological specimen container, the apparatus comprising: a fitting sized and shaped to couple with the sealing aperture of the sample container, the fitting comprising an internal cavity for allowing fluid communication between a first end and a second end of the internal cavity; a perforator configured to irreversibly sever and open the openable fluid-tight seal in the sealed aperture of the sample container by coupling the fitment to the aperture and connect the first end of the lumen to the fluid headspace of the sample container; and A user replaceable sealing housing sized and shaped to receive at least one biological specimen growth indicator at the second end of the lumen, the sealing housing being selectively user engageable to restrict fluid from escaping the second end of the accessory lumen after the piercer opens the seal.

2. The device according to claim 1, comprising the at least one biological sample growth indicator arranged to be enclosed by the sealed housing separately from the surrounding environment outside the sample container.

3. The device of claim 2, wherein the at least one biological sample growth indicator comprises a biological culture medium arranged to contact fluid from the sample container via liquid travel from the sample container through the inner cavity.

4. The apparatus of claim 2, wherein the at least one biological specimen growth indicator comprises a gas sensor, the gas sensor comprising at least one of: A field effect transistor (FET) comprising at least one of: Carbon nanotubes (CNFETs); Silicon carbide (SiCFET); Metal oxide silicon (MOSFET); Graphene (GFET); Transition metal dichalcogenides (TMDFET); or Black phosphorus (BPFET); camera; Spectral imaging sensors; Hyperspectral imaging sensors; Colorimetric imaging sensors; Fluorescence responsive imaging sensors; or A chrominance sensor or a chrominance sensor array.

5. The device of claim 1, wherein the perforator comprises a seal expander sized and shaped to irreversibly sever the openable seal of the sample container, thereby displacing more than 20% of the surface area of ​​the openable seal.

6. The apparatus of claim 1, wherein the sealed housing comprises a removable cover configured to removably couple with the coupling feature of the accessory.

7. The device of claim 1, wherein the lumen comprises a cross-sectional diameter greater than 3 millimeters (mm).

8. The device of claim 1, wherein the device comprises an internal fluid sensor for measuring at least one fluid condition within at least one of the lumen or the sample container.

9. The device of claim 8, wherein the device comprises electrical contacts located outside the sample container and electrically coupled to the internal fluid sensor, the electrical contacts being configured to transmit internal fluid sensor data to an external location when the sealed housing is engaged.

10. The device of claim 1, wherein at least one of the fitment or the sealed housing is formed of at least one of a translucent or transparent material to allow imaging into the sample container when the sealed housing is engaged.

11. A system for gas sensing of a biological sample, the system comprising: a first chamber configured to receive the biological sample therein; and a gas sensing unit sized and shaped to be coupled to the first chamber and to be separated from the first chamber by a movable separator to transition from a first state to a second state upon opening of the movable separator to allow gas to enter from the first chamber for sensing by a gas sensor included in the gas sensing unit when a biological sample is located in the first chamber, wherein the gas sensor is isolated from an ambient environment surrounding the chamber in at least the second state.

12. The system of claim 11 further comprising a chamber plug sized and shaped to be removably coupled to the opening of the first chamber, wherein the gas sensing unit is sized and shaped to replace the chamber plug when the gas sensing unit is coupled to the first chamber.

13. The system of claim 12, in combination with the chamber plug changer, the chamber plug changer configured to remove a chamber plug from the opening of the first chamber and replace the chamber plug with the gas sensing unit.

14. The system of claim 11, wherein the gas sensing unit comprises: a second chamber, carrying the gas sensor; and A fluid conduit may be coupled between the first chamber and the second chamber and configured to transfer fluid from the first chamber to the second chamber.

15. The system of claim 14, wherein the conduit is included in a siphon to introduce fluid from the first chamber into the second chamber.

16. The system of claim 14, wherein the conduit is fluidly couplable with a pump to introduce fluid from the first chamber into the second chamber.

17. A method for providing access to a biological specimen container, the method comprising: coupling a fitment of a size and shape to a sealing aperture of a sample container, the coupling comprising providing fluid communication between a first end and a second end of an interior cavity of the fitment; irreversibly severing and opening a releasable fluid-tight seal in a sealed aperture of the sample container by a seal piercer connected to the fitting during coupling of the fitting to the aperture; connecting a first end of the lumen to a fluid headspace of the sample container; as well as Fluid is restricted from escaping the second end of the fitting lumen after the piercer breaks the seal by engaging a user-replaceable sealing housing sized and shaped to receive at least one biological specimen growth indicator at the second end of the lumen.

18. The method of claim 17, comprising arranging the at least one biological sample growth indicator to be enclosed by the sealed enclosure separately from an ambient environment external to the sample container.

19. The method of claim 18, wherein the at least one biological specimen growth indicator comprises a biological culture medium arranged to contact fluid from the specimen container via liquid travel from the specimen container through the lumen.

20. The method of claim 18, wherein the at least one biological specimen growth indicator comprises a gas sensor, the gas sensor comprising at least one of: A field effect transistor (FET) comprising at least one of: Carbon nanotubes (CNFET); Silicon carbide (SiCFET); Metal oxide silicon (MOSFET); Graphene (GFET); Transition metal dichalcogenides (TMDFET); or Black phosphorus (BPFET); camera; Spectral imaging sensors; Hyperspectral imaging sensors; Colorimetric imaging sensors; Fluorescence responsive imaging sensors; or A chrominance sensor or a chrominance sensor array.

21. The method of claim 17, comprising expanding the openable seal of the sample container to displace more than 20% of the surface area of ​​the openable seal.

22. The method of claim 17, comprising: providing an internal fluid sensor at a location within at least one of the sample container or the fitment; and At least one fluid condition within at least one of the lumen or the sample container is measured by the internal fluid sensor.

23. The method according to claim 22, comprising: providing an electrical contact located on the exterior of the sample container and electrically coupled to the internal fluid sensor; and When the sealed housings are engaged, the internal fluid sensor data is transmitted to an external location via contacts.

Images